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Double-stranded RNA-dependent Protein Kinase (pkr) Is Essential for Thermotolerance, Accumulation of HSP70, and Stabilization of ARE-containing HSP70 mRNA during Stress

Zhao, Meijuan and Tang, Dan and Lechpammer, Stanislav and Hoffman, Alexander and Asea, Alexzander and Stevenson, Mary Ann and Catherwood, Stuart K. (2002) Double-stranded RNA-dependent Protein Kinase (pkr) Is Essential for Thermotolerance, Accumulation of HSP70, and Stabilization of ARE-containing HSP70 mRNA during Stress. Journal of Biological Chemistry, 277 (46). pp. 44539-44547. ISSN 0021-9258. https://resolver.caltech.edu/CaltechAUTHORS:ZHAjbc02

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Abstract

We have investigated the role of the double-stranded RNA-dependent protein kinase gene (pkr) in the regulation of the heat shock response. We show that the pkr gene is essential for efficient activation of the heat shock response and that pkr disruption profoundly inhibits heat shock protein 70 (HSP70) synthesis and blocks the development of thermotolerance. Despite these profound effects, pkr disruption did not markedly affect the activation of heat shock factor 1 by heat and did not reduce the rate of transcription of the HSP70 gene after heat shock. However, despite the lack of effect of pkr disruption on HSP70 gene transcription, we found a significant decrease in the expression of HSP70 mRNA in pkr-/- cells after heat shock. Kinetic studies of mRNA turnover suggested a block in the thermal stabilization of HSP70 mRNA in pkr-/- cells. As the thermal stabilization of HSP70 mRNA is thought to involve cis-acting A+U rich (ARE) elements in the 3'-untranslated region (UTR), we examined a potential role for pkr in this process. We found that a reporter beta-galactosidase mRNA destabilized by introduction of a functional ARE into the 3'-UTR became stabilized by heat but only in cells containing an intact pkr gene. Our studies suggest therefore that pkr plays a significant role in the stabilization of mRNA species containing ARE destruction sequences in the 3'-UTR and through this mechanism, contributes to the regulation of the heat shock response and other processes.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1074/jbc.M208408200DOIUNSPECIFIED
Additional Information:© 2002 The American Society for Biochemistry and Molecular Biology, Inc. Received for publication, August 16, 2002. Published, JBC Papers in Press, August 30, 2002, DOI 10.1074/jbc.M208408200. We thank Dr. Robert J. Schneider (New York University, School of Medicine) for the kind gift of the AU-beta -Gal reporter plasmids. This work was supported by National Institutes of Health Grants CA47407-11, CA83890-01, and CA77465 (to S. K. C.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Funding AgencyGrant Number
IHCA47407-11
NIHCA83890-01
NIHCA77465
Issue or Number:46
Record Number:CaltechAUTHORS:ZHAjbc02
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:ZHAjbc02
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6202
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:28 Nov 2006
Last Modified:02 Oct 2019 23:30

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